Comprehensive electrocardiographic diagnosis based on deep learning

Cardiovascular disease (CVD) is the leading cause of death worldwide, and coronary artery disease (CAD) is a major contributor. Early-stage CAD can progress if undiagnosed and left untreated, leading to myocardial infarction (MI) that may induce irreversible heart muscle damage, resulting in heart chamber remodeling and eventual congestive heart failure (CHF). Electrocardiography (ECG) signals can be useful to detect established MI, and may also be helpful for early diagnosis of CAD. For the latter especially, the ECG perturbations can be subtle and potentially misclassified on manual interpretation and/or when analyzed by traditional algorithms found in ECG instrumentation. For automated diagnostic systems (ADS), deep learning techniques are favored over conventional machine learning techniques, due to the automatic feature extraction and selection processes involved. This paper highlights various deep learning algorithms exploited for the classification of ECG signals into CAD, MI, and CHF conditions. The Convolutional Neural Network (CNN), followed by combined CNN and Long Short-Term Memory (LSTM) models, appear to be the most useful architectures for classification. A 16-layer LSTM model was developed in our study and validated using 10-fold cross validation. A classification accuracy of 98.5% was achieved. Our proposed model has the potential to be a useful diagnostic tool in hospitals for the classification of abnormal ECG signals

Design, Evaluation, and Application of Heart Rate Variability Analysis Software (HRVAS)

The analysis of heart rate variability (HRV) has become an increasingly popular and important tool for studying many disease pathologies in the past twenty years. HRV analyses are methods used to non-invasively quantify variability within heart rate. Purposes of this study were to design, evaluate, and apply an easy to use and open-source HRV analysis software package (HRVAS). HRVAS implements four major categories of HRV techniques: statistical and time-domain analysis, frequency-domain analysis, nonlinear analysis, and time-frequency analysis. Software evaluations were accomplished by performing HRV analysis on simulated and public congestive heart failure (CHF) data. Application of HRVAS included studying the effects of hyperaldosteronism on HRV in rats. Simulation and CHF results demonstrated that HRVAS was a dependable HRV analysis tool. Results from the rat hyperaldosteronism model showed that 5 of 26 HRV measures were statistically significant (p\u3c0.05). HRVAS provides a useful tool for HRV analysis to researchers

ECG analysis and classification using CSVM, MSVM and SIMCA classifiers

Reliable ECG classification can potentially lead to better detection methods and increase accurate diagnosis of arrhythmia, thus improving quality of care. This thesis investigated the use of two novel classification algorithms: CSVM and SIMCA, and assessed their performance in classifying ECG beats. The project aimed to introduce a new way to interactively support patient care in and out of the hospital and develop new classification algorithms for arrhythmia detection and diagnosis. Wave (P-QRS-T) detection was performed using the WFDB Software Package and multiresolution wavelets. Fourier and PCs were selected as time-frequency features in the ECG signal; these provided the input to the classifiers in the form of DFT and PCA coefficients. ECG beat classification was performed using binary SVM. MSVM, CSVM, and SIMCA; these were subsequently used for simultaneously classifying either four or six types of cardiac conditions. Binary SVM classification with 100% accuracy was achieved when applied on feature-reduced ECG signals from well-established databases using PCA. The CSVM algorithm and MSVM were used to classify four ECG beat types: NORMAL, PVC, APC, and FUSION or PFUS; these were from the MIT-BIH arrhythmia database (precordial lead group and limb lead II). Different numbers of Fourier coefficients were considered in order to identify the optimal number of features to be presented to the classifier. SMO was used to compute hyper-plane parameters and threshold values for both MSVM and CSVM during the classifier training phase. The best classification accuracy was achieved using fifty Fourier coefficients. With the new CSVM classifier framework, accuracies of 99%, 100%, 98%, and 99% were obtained using datasets from one, two, three, and four precordial leads, respectively. In addition, using CSVM it was possible to successfully classify four types of ECG beat signals extracted from limb lead simultaneously with 97% accuracy, a significant improvement on the 83% accuracy achieved using the MSVM classification model. In addition, further analysis of the following four beat types was made: NORMAL, PVC, SVPB, and FUSION. These signals were obtained from the European ST-T Database. Accuracies between 86% and 94% were obtained for MSVM and CSVM classification, respectively, using 100 Fourier coefficients for reconstructing individual ECG beats. Further analysis presented an effective ECG arrhythmia classification scheme consisting of PCA as a feature reduction method and a SIMCA classifier to differentiate between either four or six different types of arrhythmia. In separate studies, six and four types of beats (including NORMAL, PVC, APC, RBBB, LBBB, and FUSION beats) with time domain features were extracted from the MIT-BIH arrhythmia database and the St Petersburg INCART 12-lead Arrhythmia Database (incartdb) respectively. Between 10 and 30 PCs, coefficients were selected for reconstructing individual ECG beats in the feature selection phase. The average classification accuracy of the proposed scheme was 98.61% and 97.78 % using the limb lead and precordial lead datasets, respectively. In addition, using MSVM and SIMCA classifiers with four ECG beat types achieved an average classification accuracy of 76.83% and 98.33% respectively. The effectiveness of the proposed algorithms was finally confirmed by successfully classifying both the six beat and four beat types of signal respectively with a high accuracy ratio

Automatic analysis and classification of cardiac acoustic signals for long term monitoring

Objective: Cardiovascular diseases are the leading cause of death worldwide resulting in over 17.9 million deaths each year. Most of these diseases are preventable and treatable, but their progression and outcomes are significantly more positive with early-stage diagnosis and proper disease management. Among the approaches available to assist with the task of early-stage diagnosis and management of cardiac conditions, automatic analysis of auscultatory recordings is one of the most promising ones, since it could be particularly suitable for ambulatory/wearable monitoring. Thus, proper investigation of abnormalities present in cardiac acoustic signals can provide vital clinical information to assist long term monitoring. Cardiac acoustic signals, however, are very susceptible to noise and artifacts, and their characteristics vary largely with the recording conditions which makes the analysis challenging. Additionally, there are challenges in the steps used for automatic analysis and classification of cardiac acoustic signals. Broadly, these steps are the segmentation, feature extraction and subsequent classification of recorded signals using selected features. This thesis presents approaches using novel features with the aim to assist the automatic early-stage detection of cardiovascular diseases with improved performance, using cardiac acoustic signals collected in real-world conditions. Methods: Cardiac auscultatory recordings were studied to identify potential features to help in the classification of recordings from subjects with and without cardiac diseases. The diseases considered in this study for the identification of the symptoms and characteristics are the valvular heart diseases due to stenosis and regurgitation, atrial fibrillation, and splitting of fundamental heart sounds leading to additional lub/dub sounds in the systole or diastole interval of a cardiac cycle. The localisation of cardiac sounds of interest was performed using an adaptive wavelet-based filtering in combination with the Shannon energy envelope and prior information of fundamental heart sounds. This is a prerequisite step for the feature extraction and subsequent classification of recordings, leading to a more precise diagnosis. Localised segments of S1 and S2 sounds, and artifacts, were used to extract a set of perceptual and statistical features using wavelet transform, homomorphic filtering, Hilbert transform and mel-scale filtering, which were then fed to train an ensemble classifier to interpret S1 and S2 sounds. Once sound peaks of interest were identified, features extracted from these peaks, together with the features used for the identification of S1 and S2 sounds, were used to develop an algorithm to classify recorded signals. Overall, 99 features were extracted and statistically analysed using neighborhood component analysis (NCA) to identify the features which showed the greatest ability in classifying recordings. Selected features were then fed to train an ensemble classifier to classify abnormal recordings, and hyperparameters were optimized to evaluate the performance of the trained classifier. Thus, a machine learning-based approach for the automatic identification and classification of S1 and S2, and normal and abnormal recordings, in real-world noisy recordings using a novel feature set is presented. The validity of the proposed algorithm was tested using acoustic signals recorded in real-world, non-controlled environments at four auscultation sites (aortic valve, tricuspid valve, mitral valve, and pulmonary valve), from the subjects with and without cardiac diseases; together with recordings from the three large public databases. The performance metrics of the methodology in relation to classification accuracy (CA), sensitivity (SE), precision (P+), and F1 score, were evaluated. Results: This thesis proposes four different algorithms to automatically classify fundamental heart sounds – S1 and S2; normal fundamental sounds and abnormal additional lub/dub sounds recordings; normal and abnormal recordings; and recordings with heart valve disorders, namely the mitral stenosis (MS), mitral regurgitation (MR), mitral valve prolapse (MVP), aortic stenosis (AS) and murmurs, using cardiac acoustic signals. The results obtained from these algorithms were as follows: • The algorithm to classify S1 and S2 sounds achieved an average SE of 91.59% and 89.78%, and F1 score of 90.65% and 89.42%, in classifying S1 and S2, respectively. 87 features were extracted and statistically studied to identify the top 14 features which showed the best capabilities in classifying S1 and S2, and artifacts. The analysis showed that the most relevant features were those extracted using Maximum Overlap Discrete Wavelet Transform (MODWT) and Hilbert transform. • The algorithm to classify normal fundamental heart sounds and abnormal additional lub/dub sounds in the systole or diastole intervals of a cardiac cycle, achieved an average SE of 89.15%, P+ of 89.71%, F1 of 89.41%, and CA of 95.11% using the test dataset from the PASCAL database. The top 10 features that achieved the highest weights in classifying these recordings were also identified. • Normal and abnormal classification of recordings using the proposed algorithm achieved a mean CA of 94.172%, and SE of 92.38%, in classifying recordings from the different databases. Among the top 10 acoustic features identified, the deterministic energy of the sound peaks of interest and the instantaneous frequency extracted using the Hilbert Huang-transform, achieved the highest weights. • The machine learning-based approach proposed to classify recordings of heart valve disorders (AS, MS, MR, and MVP) achieved an average CA of 98.26% and SE of 95.83%. 99 acoustic features were extracted and their abilities to differentiate these abnormalities were examined using weights obtained from the neighborhood component analysis (NCA). The top 10 features which showed the greatest abilities in classifying these abnormalities using recordings from the different databases were also identified. The achieved results demonstrate the ability of the algorithms to automatically identify and classify cardiac sounds. This work provides the basis for measurements of many useful clinical attributes of cardiac acoustic signals and can potentially help in monitoring the overall cardiac health for longer duration. The work presented in this thesis is the first-of-its-kind to validate the results using both, normal and pathological cardiac acoustic signals, recorded for a long continuous duration of 5 minutes at four different auscultation sites in non-controlled real-world conditions.Open Acces

Statistical and Graph-Based Signal Processing: Fundamental Results and Application to Cardiac Electrophysiology

The goal of cardiac electrophysiology is to obtain information about the mechanism, function, and performance of the electrical activities of the heart, the identification of deviation from normal pattern and the design of treatments. Offering a better insight into cardiac arrhythmias comprehension and management, signal processing can help the physician to enhance the treatment strategies, in particular in case of atrial fibrillation (AF), a very common atrial arrhythmia which is associated to significant morbidities, such as increased risk of mortality, heart failure, and thromboembolic events. Catheter ablation of AF is a therapeutic technique which uses radiofrequency energy to destroy atrial tissue involved in the arrhythmia sustenance, typically aiming at the electrical disconnection of the of the pulmonary veins triggers. However, recurrence rate is still very high, showing that the very complex and heterogeneous nature of AF still represents a challenging problem. Leveraging the tools of non-stationary and statistical signal processing, the first part of our work has a twofold focus: firstly, we compare the performance of two different ablation technologies, based on contact force sensing or remote magnetic controlled, using signal-based criteria as surrogates for lesion assessment. Furthermore, we investigate the role of ablation parameters in lesion formation using the late-gadolinium enhanced magnetic resonance imaging. Secondly, we hypothesized that in human atria the frequency content of the bipolar signal is directly related to the local conduction velocity (CV), a key parameter characterizing the substrate abnormality and influencing atrial arrhythmias. Comparing the degree of spectral compression among signals recorded at different points of the endocardial surface in response to decreasing pacing rate, our experimental data demonstrate a significant correlation between CV and the corresponding spectral centroids. However, complex spatio-temporal propagation pattern characterizing AF spurred the need for new signals acquisition and processing methods. Multi-electrode catheters allow whole-chamber panoramic mapping of electrical activity but produce an amount of data which need to be preprocessed and analyzed to provide clinically relevant support to the physician. Graph signal processing has shown its potential on a variety of applications involving high-dimensional data on irregular domains and complex network. Nevertheless, though state-of-the-art graph-based methods have been successful for many tasks, so far they predominantly ignore the time-dimension of data. To address this shortcoming, in the second part of this dissertation, we put forth a Time-Vertex Signal Processing Framework, as a particular case of the multi-dimensional graph signal processing. Linking together the time-domain signal processing techniques with the tools of GSP, the Time-Vertex Signal Processing facilitates the analysis of graph structured data which also evolve in time. We motivate our framework leveraging the notion of partial differential equations on graphs. We introduce joint operators, such as time-vertex localization and we present a novel approach to significantly improve the accuracy of fast joint filtering. We also illustrate how to build time-vertex dictionaries, providing conditions for efficient invertibility and examples of constructions. The experimental results on a variety of datasets suggest that the proposed tools can bring significant benefits in various signal processing and learning tasks involving time-series on graphs. We close the gap between the two parts illustrating the application of graph and time-vertex signal processing to the challenging case of multi-channels intracardiac signals

Electronic devices and systems for monitoring of diabetes and cardiovascular diseases

Diabetes is a serious chronic disease which causes a high rate of morbidity and mortality all over the world. In 2007, more than 246 million people suffered from diabetes worldwide and unfortunately the incidence of diabetes is increasing at alarming rates. The number of people with diabetes is expected to double within the next 25 years due to a combination of population ageing, unhealthy diets, obesity and sedentary lifestyles. It can lead to blindness, heart disease, stroke, kidney failure, amputations and nerve damage. In women, diabetes can cause problems during pregnancy and make it more likely for the baby to be born with birth defects. Moreover, statistical analysis shows that 75% of diabetic patients die prematurely of cardiovascular disease (CVD). The absolute risk of cardiovascular disease in patients with type 1 (insulin-dependent) diabetes is lower than that in patients with type 2 (non-insulin-dependent) diabetes, in part because of their younger age and the lower prevalence of CVD risk factors, and in part because of the different pathophysiology of the two diseases. Unfortunately, about 9 out of 10 people with diabetes have type 2 diabetes. For these reasons, cardiopathes and diabetic patients need to be frequently monitored and in some cases they could easily perform at home the requested physiological measurements (i.e. glycemia, heart rate, blood pressure, body weight, and so on) sending the measured data to the care staff in the hospital. Several researches have been presented over the last years to address these issues by means of digital communication systems. The largest part of such works uses a PC or complex hardware/software systems for this purpose. Beyond the cost of such systems, it should be noted that they can be quite accessible by relatively young people but the same does not hold for elderly patients more accustomed to traditional equipments for personal entertainment such as TV sets. Wearable devices can permit continuous cardiovascular monitoring both in clinical settings and at home. Benefits may be realized in the diagnosis and treatment of a number of major 15 diseases. In conjunction with appropriate alarm algorithms, they can increase surveillance capabilities for CVD catastrophe for high-risk subjects. Moreover, they could play an important role in the wireless surveillance of people during hazardous operations (military, fire-fighting, etc.) or during sport activities. For patients with chronic cardiovascular disease, such as heart failure, home monitoring employing wearable device and tele-home care systems may detect exacerbations in very early stages or at dangerous levels that necessitate an emergency room visit and an immediate hospital admission. Taking into account mains principles for the design of good wearable devices and friendly tele-home care systems, such as safety, compactness, motion and other disturbance rejection, data storage and transmission, low power consumption, no direct doctor supervision, it is imperative that these systems are easy to use and comfortable to wear for long periods of time. The aim of this work is to develop an easy to use tele-home care system for diabetes and cardiovascular monitoring, well exploitable even by elderly people, which are the main target of a telemedicine system, and wearable devices for long term measuring of some parameters related to sleep apnoea, heart attack, atrial fibrillation and deep vein thrombosis. Since set-top boxes for Digital Video Broadcast Terrestrial (DVB-T) are in simple computers with their Operating System, a Java Virtual Machine, a modem for the uplink connection and a set of standard ports for the interfacing with external devices, elderly, diabetics and cardiopathes could easily send their self-made exam to the care staff placed elsewhere. The wearable devices developed are based on the well known photopletysmographic method which uses a led source/detector pair applied on the skin in order to obtain a biomedical signal related to the volume and percentage of oxygen in blood. Such devices investigate the possibility to obtain more information to those usually obtained by this technique (heart rate and percentage of oxygen saturation) in order to discover new algorithms for the continuous and remote or in ambulatory monitoring and screening of sleep apnoea, heart attack, atrial fibrillation and deep vein thrombosis

Breathing pattern characterization in patients with respiratory and cardiac failure

El objetivo principal de la tesis es estudiar los patrones respiratorios de pacientes en proceso de extubación y pacientes con insuficiencia cardiaca crónica (CHF), a partirde la señal de flujo respiratorio. La información obtenida de este estudio puede contribuir a la comprensión de los procesos fisiológicos subyacentes,y ayudar en el diagnóstico de estos pacientes. Uno de los problemas más desafiantes en unidades de cuidados intensivos es elproceso de desconexión de pacientes asistidos mediante ventilación mecánica. Más del 10% de pacientes que se extuban tienen que ser reintubados antes de 48 horas. Una prueba fallida puede ocasionar distrés cardiopulmonar y una mayor tasa de mortalidad. Se caracterizó el patrón respiratorio y la interacción dinámica entre la frecuenciacardiaca y frecuencia respiratoria, para obtener índices no invasivos que proporcionen una mayor información en el proceso de destete y mejorar el éxito de la desconexión.Las señales de flujo respiratorio y electrocardiográfica utilizadas en este estudio fueron obtenidas durante 30 minutos aplicando la prueba de tubo en T. Se compararon94 pacientes que tuvieron éxito en el proceso de extubación (GE), 39 pacientes que fracasaron en la prueba al mantener la respiración espontánea (GF), y 21 pacientes quesuperaron la prueba con éxito y fueron extubados, pero antes de 48 horas tuvieron que ser reintubados (GR). El patrón respiratorio se caracterizó a partir de las series temporales. Se aplicó la dinámica simbólica conjunta a las series correspondientes a las frecuencias cardiaca y respiratoria, para describir las interacciones cardiorrespiratoria de estos pacientes. Técnicas de "clustering", ecualización del histograma, clasificación mediante máquinasde soporte vectorial (SVM) y técnicas de validación permitieron seleccionar el conjunto de características más relevantes. Se propuso una nueva métrica B (índice de equilibrio) para la optimización de la clasificación con muestras desbalanceadas. Basado en este nuevo índice, aplicando SVM, se seleccionaron las mejores características que mantenían el mejor equilibrio entre sensibilidad y especificidad en todas las clasificaciones. El mejor resultado se obtuvo considerando conjuntamente la precisión y el valor de B, con una clasificación del 80% entre los grupos GE y GF, con 6 características. Clasificando GE vs. el resto de los pacientes, el mejor resultado se obtuvo con 9 características, con 81%. Clasificando GR vs. GE y GR vs. el resto de pacientes la precisión fue del 83% y 81% con 9 y 10 características, respectivamente. La tasa de mortalidad en pacientes con CHF es alta y la estratificación de estospacientes en función del riesgo es uno de los principales retos de la cardiología contemporánea. Estos pacientes a menudo desarrollan patrones de respiraciónperiódica (PB) incluyendo la respiración de Cheyne-Stokes (CSR) y respiración periódica sin apnea. La respiración periódica en estos pacientes se ha asociadocon una mayor mortalidad, especialmente en pacientes con CSR. Por lo tanto, el estudio de estos patrones respiratorios podría servir como un marcador de riesgo y proporcionar una mayor información sobre el estado fisiopatológico de pacientes con CHF. Se pretende identificar la condición de los pacientes con CHFde forma no invasiva mediante la caracterización y clasificación de patrones respiratorios con PBy respiración no periódica (nPB), y patrón de sujetos sanos, a partir registros de 15minutos de la señal de flujo respiratorio. Se caracterizó el patrón respiratorio mediante un estudio tiempo-frecuencia estacionario y no estacionario, de la envolvente de la señal de flujo respiratorio. Parámetros relacionados con la potencia espectral de la envolvente de la señal presentaron losmejores resultados en la clasificación de sujetos sanos y pacientes con CHF con CSR, PB y nPB. Las curvas ROC validan los resultados obtenidos. Se aplicó la "correntropy" para una caracterización tiempo-frecuencia mas completa del patrón respiratorio de pacientes con CHF. La "corretronpy" considera los momentos estadísticos de orden superior, siendo más robusta frente a los "outliers". Con la densidad espectral de correntropy (CSD) tanto la frecuencia de modulación como la dela respiración se representan en su posición real en el eje frecuencial. Los pacientes con PB y nPB, presentan diferentesgrados de periodicidad en función de su condición, mientras que los sujetos sanos no tienen periodicidad marcada. Con único parámetro se obtuvieron resultados del 88.9% clasificando pacientes PB vs. nPB, 95.2% para CHF vs. sanos, 94.4% para nPB vs. sanos.The main objective of this thesis is to study andcharacterize breathing patterns through the respiratory flow signal applied to patients on weaning trials from mechanicalventilation and patients with chronic heart failure (CHF). The aim is to contribute to theunderstanding of the underlying physiological processes and to help in the diagnosis of these patients. One of the most challenging problems in intensive care units is still the process ofdiscontinuing mechanical ventilation, as over 10% of patients who undergo successfulT-tube trials have to be reintubated in less than 48 hours. A failed weaning trial mayinduce cardiopulmonary distress and carries a higher mortality rate. We characterize therespiratory pattern and the dynamic interaction between heart rate and breathing rate toobtain noninvasive indices that provide enhanced information about the weaningprocess and improve the weaning outcome. This is achieved through a comparison of 94 patients with successful trials (GS), 39patients who fail to maintain spontaneous breathing (GF), and 21 patients who successfully maintain spontaneous breathing and are extubated, but require thereinstitution of mechanical ventilation in less than 48 hours because they are unable tobreathe (GR). The ECG and the respiratory flow signals used in this study were acquired during T-tube tests and last 30 minute. The respiratory pattern was characterized by means of a number of respiratory timeseries. Joint symbolic dynamics applied to time series of heart rate and respiratoryfrequency was used to describe the cardiorespiratory interactions of patients during theweaning trial process. Clustering, histogram equalization, support vector machines-based classification (SVM) and validation techniques enabled the selection of the bestsubset of input features. We defined a new optimization metric for unbalanced classification problems, andestablished a new SVM feature selection method, based on this balance index B. The proposed B-based SVM feature selection provided a better balance between sensitivityand specificity in all classifications. The best classification result was obtained with SVM feature selection based on bothaccuracy and the balance index, which classified GS and GFwith an accuracy of 80%, considering 6 features. Classifying GS versus the rest of patients, the best result wasobtained with 9 features, 81%, and the accuracy classifying GR versus GS, and GR versus the rest of the patients was 83% and 81% with 9 and 10 features, respectively.The mortality rate in CHF patients remains high and risk stratification in these patients isstill one of the major challenges of contemporary cardiology. Patients with CHF oftendevelop periodic breathing patterns including Cheyne-Stokes respiration (CSR) and periodic breathing without apnea. Periodic breathing in CHF patients is associated withincreased mortality, especially in CSR patients. Therefore it could serve as a risk markerand can provide enhanced information about thepathophysiological condition of CHF patients. The main goal of this research was to identify CHF patients' condition noninvasively bycharacterizing and classifying respiratory flow patterns from patients with PB and nPBand healthy subjects by using 15-minute long respiratory flow signals. The respiratory pattern was characterized by a stationary and a nonstationary time-frequency study through the envelope of the respiratory flow signal. Power-related parameters achieved the best results in all of the classifications involving healthy subjects and CHF patients with CSR, PB and nPB and the ROC curves validated theresults obtained for the identification of different respiratory patterns. We investigated the use of correntropy for the spectral characterization of respiratory patterns in CHF patients. The correntropy function accounts for higher-order moments and is robust to outliers. Due to the former property, the respiratory and modulationfrequencies appear at their actual locations along the frequency axis in the correntropy spectral density (CSD). The best results were achieved with correntropy and CSD-related parameters that characterized the power in the modulation and respiration discriminant bands, definedas a frequency interval centred on the modulation and respiration frequency peaks,respectively. All patients, i.e. both PB and nPB, exhibit various degrees of periodicitydepending on their condition, whereas healthy subjects have no pronounced periodicity.This fact led to excellent results classifying PB and nPB patients 88.9%, CHF versushealthy 95.2%, and nPB versus healthy 94.4% with only one parameter.Postprint (published version

Time-frequency investigation of heart rate variability and cardiovascular system modeling of normal and chronic obstructive pulmonary disease (COPD) subjects

A study has been designed to add insight to some questions that have not been fully investigated in the heart rate variability field and the cardiovascular regulation system in normal and Chronic Obstructive Pulmonary Disease (COPD) subjects. It explores the correlations between heart rate variability and cardiovascular regulation, which interact through complex multiple feedback and control loops. This work examines the coupling between heart rate (HR), respiration (RESP), and blood pressure (BP) via closed-loop system identification techniques in order to noninvasively assess the underlying physiology. In the first part of the study, the applications of five different bilinear time-frequency representations are evaluated on modeled HRV test signals, actual electrocardiograms (ECG), BP and RESP signals. Each distribution: the short time Fourier transform (STFT), the smoothed pseudo Wigner-Ville (SPWVD), the ChoiWilliams (CWD), the Bom-Jordan-Cohen (BJC) and wavelet distribution (WL), has unique characteristics which is shown to affect the amount of smoothing and the generation of cross-terms. The CWD and the WL are chosen for further application because of overcoming the drawbacks of other distributions by providing higher resolution in time and frequency while suppressing interferences between the signal components. In the second part of the study, the Morlet, Meyer, Daubechies 4, Mexican Hat and Haar wavelets are used to investigate the heart rate and blood pressure variability from both COPD and normal subjects. The results of wavelet analysis give much more useful information than the Cohen\u27s class representations. Here we are able to quantitatively assess the parasympathetic (HF) and sympatho-vagal balance (LF:HF) changes as a function of time. As a result, COPD subjects breathe faster, have higher blood pressure variability and lower HRV. In the third part of the study, a special class of the exogenous autoregressive (ARX) model is developed as an analytical tool for uncovering the hidden autonomic control processes. Non-parametric relationships between the input and outputs of the ARX model resulting in transfer function estimations of the noise filters and the input filter were used as mechanistic cardiovascular models that have shown to have predictive capabilities for the underlying autonomic nervous system activity of COPD patients. Transfer functions of COPD cardiovascular models have similar DC gains but show a larger lag in phase as compared to the models of normal subjects. Finally, a method of severity classification is presented. This method combines the techniques of principal component analysis (PCA) and cluster analysis (CA) and has been shown to separate the COPD from the normal population with 100% accuracy. It can also classify the COPD population into at risk , mild , moderate and severe stages with 100%, 90%, 88% and 100% accuracy respectively. As a result, cluster and principal component analysis can be used to separate COPD and normal subjects and can be used successfully in COPD severity classification

Analysis of Atrial Electrograms

This work provides methods to measure and analyze features of atrial electrograms - especially complex fractionated atrial electrograms (CFAEs) - mathematically. Automated classification of CFAEs into clinical meaningful classes is applied and the newly gained electrogram information is visualized on patient specific 3D models of the atria. Clinical applications of the presented methods showed that quantitative measures of CFAEs reveal beneficial information about the underlying arrhythmia